Positioning TERT at the apex of aging.

Aging is a biologically tractable process. Telomerase reverse transcriptase (TERT) has emerged as an upstream regulator coordinating several hallmarks of aging across preclinical models. Beyond maintaining telomeres, TERT influences mitochondrial health, epigenetic regulation, inflammation and stem cell function. Multiple translational strategies are being explored to modulate TERT. In mice and human cell models, restoration of physiological-range TERT expression characteristic of younger cells, or related telomere-focused interventions, has been associated with improvements in selected age-related phenotypes without a detectable increase in cancer. Simultaneously, human genetics links common variation in the TERT locus to increased risk of several cancers, underscoring the need for careful mechanistic and long-term safety evaluations. Together, mounting evidence indicates that TERT occupies an important position in aging biology with the potential to affect healthspan. This Perspective reviews current evidence for TERT's canonical and noncanonical roles and outlines a cautious therapeutic framework for evaluating TERT-directed geroprotective strategies.